Two-pore channel proteins, TPC1 and TPC2, are calcium permeable ion channels found localized to the membranes of endolysosomal calcium stores. There is increasing interest in the role of TPC-mediated intracellular signaling in various pathologies; however their role in breast cancer has not been extensively evaluated. TPC1 and TPC2 mRNA was present in all non-tumorigenic and tumorigenic breast cell lines assessed. Silencing of TPC2 but not TPC1 attenuated epidermal growth factor-induced vimentin expression in MDA-MB-468 breast cancer cells. This effect was not due to a general inhibition of epithelial to mesenchymal transition (EMT) as TPC2 silencing had no effect on epidermal growth factor (EGF)-induced changes on E-cadherin expression. TPC1 and TPC2 were also shown to differentially regulate cyclopiazonic acid (CPA)-mediated changes in cytosolic free Ca2+. These findings indicate potential differential regulation of signaling processes by TPC1 and TPC2 in breast cancer cells.
|Original language||English (US)|
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Sep 2 2016|
Bibliographical noteFunding Information:
This research was partially supported by the Australian National Health and Medical Research Council (NHMRC; project grant 1022263 ) and the Queensland Cancer Council ( 1042819 ). AHJ was funded by the Ministry of Higher Education Malaysia through the Bumiputera Training Scheme Scholarship (SLAB). TAS was funded by an NHMRC Biomedical Postgraduate Scholarship ( 1039358 ). EWT was supported in part by the National Breast Cancer Foundation (EMP athy National Collaborative Research Program, CG-10-04 ).
- Breast cancer
- Calcium signaling
- Epidermal growth factor
- Two-pore channel